Nanostructures DOI: 10.1002/anie.201203083 Microfluidic Synthesis of Palladium Nanocrystals Assisted by Supercritical CO 2 : Tailored Surface Properties for Applications in Boron Chemistry** Thomas Gendrineau, Samuel Marre, Michel Vaultier, Mathieu Pucheault,* and Cyril Aymonier* Main challenges associated with heterogeneous catalysis rely on designing flexible methods to modulate catalytic efficien- cies. [1] In that context, semi-heterogeneous catalysis [2] with metal nanocrystals (NCs) provides a nice entry into designing such materials. Indeed transition-metal NCs [3] can be pre- pared with excellent control of the physical properties including the size, nature, composition, and morphology. NCs combine high surface area, thus conferring excellent reactivity capacity, [4] with tunable surface functionalization, possibly with various ligands. In this regard, microfluidic processes turned out to be powerful tools to produce hierarchically organized multiple particles with good control over size and shape. [5] Combining specific characteristics of micronized processes with high pressure/high temperature [6] —including supercritical condi- tions [7] —leads to multiple additional advantages. Hydrody- namical parameters, heat and mass transfer, and process safety are greatly improved. [8] Inspired by previous studies of NCs synthesis using supercritical milli- and microfluidics achieved in our group, [7c, 9] the approach takes advantage of process flexibility and ability to build a small cohort of nanocatalysts stabilized by specific ligands. Herein, we report the contribution of a supercritical microfluidic process to access a library of new tunable functionalized NCs, namely a palladium core stabilized by various ligands. Those NCs were designed to catalyze reactions of broad applicability, namely Vaultier [10] and Miyaura [11] borylation and Suzuki–Miyaura cross-coupling. [12] Palladium NCs were synthesized at 100 8C and 25 MPa in a co-flow capillary microsystem (Figure 1 A). Coaxial flows appeared to be suitable for generating NCs stabilized by various organic shells, as previously demonstrated. [7c] In classical homogeneous catalysis, ligands are coordinated to Pd 0 or Pd II centers and modulate the reactivity of the complex towards a given transformation. As such, we envisioned that different catalytic activities would arise from functionaliza- tion with various ligands such as phosphanes, bisphosphanes, and N-heterocyclic carbenes. The operating conditions were controlled by an oil bath (T), a back pressure regulator (p) placed downstream in the microsystem, and three high- pressure pumps (flow rates), with the residence time being fixed at 17 seconds. The inner palladium precursor solution was flow-focused by the outer flow, which contained the ligands, therefore confining the formation of NCs to the center of the main stream with subsequent functionalization. Palladium nanocatalysts were prepared from the hydro- gen reduction of bis(hexafluoroacetylacetonate)palladi- um(II) ([Pd(hfa) 2 ]) in a toluene/CO 2 mixture, in the presence of organic stabilizers (Figure 1 A). Palladium(0) atoms were then prone to nucleation and growth processes, thus providing naked NCs. The poor solubility of hydrogen in toluene usually results in mass-transfer limitations for the palladium(II) precursor reduction. [13] This issue was overcome thanks to additional scCO 2 (Tc = 31 8C, Pc = 7.38 MPa), which greatly enhances H 2 solubility in the mixture. [14] In a second step, the surface of the palladium NCs was decorated with various ligands and collected as a colloidal solution—upon depressu- rization—for a direct application in catalysis reactions with- out further purification steps. We deliberately used ligands displaying different electronic and steric properties to eval- uate their influences on the catalytic process. Those ligands are classically employed in homogeneous catalysis for tuning stereoelectronic properties of the metal center, namely: bis(mesityl)imidazoliumchloride leading in situ to the corre- sponding N-heterocyclic carbene (NHC; NC1), [15] cyclohexyl JohnPhos (NC2), di(phenylphosphino)propane (dppp; NC3), tert-butyl XPhos (NC4), tricyclohexyl phosphane (NC5), tri(3-furyl)phosphane (NC6), 2,2’-bis(diphenylphosphino)- 1,1’-binaphthyl (binap; NC7), SPhos (NC8), 1,1’-bis(diphe- nylphosphino)ferrocene (dppf; NC9); see Figure 2. Palladium NCs complexed by dppf (NC9) were used as a reference for full characterization of the NCs. [16] The formation of organic–inorganic hybrid nanocrystals was first evidenced by high-resolution transmission electron micro- scopy (HRTEM; Figure 1 B), thus revealing the presence of small spherical palladium NCs with a narrow size distribution (3.6 Æ 0.6) nm (Figures 1 B and C). Complexation of the ligand to the palladium surface was proven by conducting 1 H, 13 C, 19 F, and 31 P NMR experiments (Figure 1 D and see the Supporting Information). 1 H NMR spectra of dppf-com- plexed NPs show signals for the cyclopentadienyl moiety at d = 4.76 and 4.30 ppm. Compared to the signals in the 1 H NMR spectra of free dppf at d = 4.27 and 4.01 ppm, [*] Dr. T. Gendrineau, Dr. S. Marre, Dr. C. Aymonier CNRS, UniversitØ de Bordeaux, ICMCB 87 avenue du Dr. Albert Schweitzer, 33608 Pessac (France) E-mail: aymonier@icmcb-bordeaux.cnrs.fr Dr. T. Gendrineau, Dr. M. Vaultier, Dr. M. Pucheault ISM, UMR CNRS 5255, UniversitØ Bordeaux 1 351 Cours de la LibØration, 33405 Talence (France) E-mail: m.pucheault@ism.u-bordeaux1.fr [**] The authors thank the GIS Advanced Materials in Aquitaine for financial support. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201203083. A ngewandte Chemi e 1 Angew. Chem. Int. Ed. 2012, 51,1–5  2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim These are not the final page numbers! Ü Ü